Fang J, Cai C, Wang Q, Lin P, Zhao Z, Cheng F
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, P.R. China.
CPT Pharmacometrics Syst Pharmacol. 2017 Mar;6(3):177-187. doi: 10.1002/psp4.12172. Epub 2017 Mar 14.
Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products.
大量癌症基因组学数据通过针对临床相关驱动基因或突变来推动精准肿瘤学的发展，从而促进了新型肿瘤药物发现模式的迅速变革。具有多药药理学特征的天然产物已被证明是开发新型癌症疗法的有前景的药物。在本研究中，我们开发了一个综合系统药理学框架，有助于在精准医学领域识别针对15种癌症类型或亚型中突变基因的潜在天然产物。我们的系统药理学框架取得了高性能。在案例研究中，我们通过针对多种癌症类型中显著突变的基因，通过计算确定了几种美国食品药品监督管理局批准或临床研究中的天然产物（如白藜芦醇、槲皮素、染料木黄酮和漆黄素）的新型抗癌适应症。总之，本研究通过利用天然产物的系统药理学，针对临床可操作的改变，为开发分子靶向癌症疗法提供了一个强大的工具。
